DISORDERED FOOD-INTAKE AND OBESITY IN RATS LACKING CHOLECYSTOKININ-A RECEPTORS

Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperg lycemia, and non-insulin-dependent diabetes mellitus and do not expres s cholecystokinin A (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In short-term feeding tests, male OLETF ra ts were completely resistant to exogenous CCK, and their response to b ombesin was attenuated. Comparisons of liquid meal consumption in OLET F and control Long-Evans Tokushima (LETO) rats demonstrated that 1) OL ETF rats had greater intakes during 30-min scheduled daytime meals and significantly larger and fewer spontaneous nighttime meals and 2) alt hough the initial rates of licking were the same, OLETF rats maintaine d the initial rate longer and the rate at which their licking declined was slower. In 24-h solid food access tests, OLETF rats consumed sign ificantly more pellets than LETO controls, and this increase was attri butable to significant increases in meal size. Together, these data ar e consistent with the interpretation that the lack of CCK-A receptors in OLETF rats results in a satiety deficit leading to increases in mea l size, overall hyperphagia, and obesity.